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Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Gengler, Simon, McClean, Paula L., McCurtin, Ruth, Gault, Victor and Holscher, Christian (2012) Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. NEUROBIOLOGY OF AGING, 33 (2). pp. 265-276. [Journal article]

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DOI: 10.1016/j.neurobiolaging.2010.02.014

Abstract

Diabetes is a risk factor for Alzheimer's disease. We tested the effects of Val(8) GLP-1, an enzyme-resistant analogue of the incretin hormone glucagon-like peptide 1 originally developed to treat diabetes in a mouse model of Alzheimer's disease that expresses mutated amyloid precursor protein (APP) and presenilin-1. We tested long term potentiation (LTP) of synaptic plasticity, inflammation response, and plaque formation. Val(8) GLP-1 crosses the blood-brain barrier when administered via intraperitoneal injection. Val(8) GLP-1 protected LTP in 9- and 18-month-old Alzheimer's disease mice when given for 3 weeks at 25 nmol/kg intraperitoneally. LTP was also enhanced in 18-month-old wild type mice, indicating that Val(8) GLP-1 also ameliorates age-related synaptic degenerative processes. Paired-pulse facilitation was also enhanced. The number of beta-amyloid plaques and microglia activation in the cortex increased with age but was not reduced by Val(8) GLP-1. In 18-month-old mice, however, the number of Congo red positive dense-core amyloid plaques was reduced. Treatment with Val(8) GLP-1 might prevent or delay neurodegenerative processes. (C) 2012 Elsevier Inc. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
Biomedical Sciences Research Institute > Molecular Medicine
ID Code:21616
Deposited By:Dr Nigel Irwin
Deposited On:28 Mar 2012 16:07
Last Modified:28 Mar 2012 16:07

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